These investigations are designed to define the role the immune system plays in the hosts interaction with antigens in the intestinal tract. Particular focus was placed on characterizing regulatory mechanisms induced in the host after exposure to antigen by the enteric route and regulatory mechanisms that control IgA production. We demonstrated a suppressor factor in the serum of erythrocyte-fed mice that was functionally indistinguishable by several criteria from a suppressor factor in the serum of mice injected with an erythrocytelysate. Both factors had the same molecular weight, were heat stable, contained immunoglobulin determinants and lacked detectable erythrocyte determinants. Suppression mediated by both factors was antigen-specific, not H-2 restricted, and inhibited IgM responses to a greater extent than IgA of IgG responses. We developed two systems to characterize regulation of the IgA response. The first system used the carbohydrate antigen dextran B1355 since mice produced IgA but not IgG anti-dextran responses to this antigen. The second system used mice multiply primed with hapten-protein conjugates since lymphoid cells from these mice can be induced to produce carrier-dependent IgA anti-hapten responses in vitro. By manipulation of the cellular components in culture, cellular regulation of the IgA response is being defined.